Heparin-induced thrombocytopenia: a frequent complication after cardiac surgery

Thrombocytopenia is a common problem in cardiovascular patients, and heparin-induced thrombocytopenia (HIT) is therefore frequently suspected. Unfractionated heparin during cardiopulmonary bypass is particularly immunogenic as 25% to 50% post-cardiac surgery patients develop heparin-dependent antibodies but only 1 to 3% will develop HIT. These antibodies recognize a 'self protein', platelet factor 4 (PF4), bound to heparin. Antibodies associated with a high risk of HIT are mainly IgG1 which strongly activate platelets and coagulation, thereby causing thrombocytopenia and thrombosis. A biphasic evolution of platelet count with a secondary decrease after a previous increase following CPB or non-recovery of thrombocytopenia within 6 days post-operatively always requires screening for HIT antibodies. Both functional (platelet activation tests) and immunologic assays (antigen assays) are necessary in every patient to establish the diagnosis of HIT. When the clinical probability of HIT is high, the first requirement is to discontinue heparin, without waiting for results of laboratory investigations. An alternative anticoagulant such as danaparoid sodium (Orgaran) or lepirudin (Refludan) must then be administered since heparin withdrawal alone is insufficient to control the prothrombotic state associated with HIT. The risk of HIT will probably soon decrease due to the wider use of fondaparinux, which does not interact in vitro with PF4, but it could remain significant in patients undergoing cardiac surgery with CPB.     

Heparin-induced thrombocytopenia

Summary Heparin-induced thrombocytopenia (HIT), next to bleeding complications, is the most important side-effect of heparin therapy in cardiac patients and the most frequently found thrombocytopenia induced by medication. Two types of HIT are distinguished on the basis of both severity of disease, and pathophysiology: type I HIT is an early, transient, clinically harmless form of thrombocytopenia, due to direct heparin-induced platelet aggregation. Thromboembolic complications are usually not seen. No treatment is required. A normalization of platelet count even if heparin is continued is a usual observation. Type II HIT is more severe than type I HIT and is frequently complicated by extension of preexisting venous thromboembolism or new arterial thrombosis. The thrombocytopenia is caused by a pathogenic heparin-dependent IgG antibody (HIT-IgG) that recognizes as its target antigen a complex consisting of heparin and platelet factor IV. Type II HIT should be suspected when the platelet count falls to less than 100,000 per cubic millimeter or less than 50% of the base line value 5 to 15 days after heparin therapy is begun, or sooner in a patient who received heparin in the recent past. The clinical diagnosis of type II HIT can be confirmed by several sensitive assays. In cases of type II HIT, heparin must be stopped immediately. However, if the patient requires continued anticoagulant therapy for an acute event such as deep venous thrombosis, substitution of an alternative rapid-acting anticoagulant drug is often needed. In the authors experience Danaparoid sodium, a low-sulfated heparinoid with a low cross-reactivity (10%) to heparin, can be regarded as an effective anticoagulant in patients with type II HIT. Preliminary experiences with intravenous recombinant hirudin are also encouraging and suggest that this direct thrombin inhibitor will emerge as a valuable alternative treatment for patients who suffer from HIT.     

The prothrombotic potential of platelet factor 4

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by heparin administration. It is caused by the formation of pathogenic antibodies to complexes of platelet factor-4 (PF4) and heparin on platelet surfaces that cause platelet activation, aggregation and thrombosis. There has been intense research on this intriguing, drug-related thrombocytopenia explaining several characteristic aspects of this condition. However, prothrombotic potential of the key player, PF4 has not been investigated in many studies although it has been shown to be critical in monocyte chemotaxis, monocyte–platelet interaction, and megakaryocyte suppression, all of which can contribute to the pathophysiology of HIT. This article explains the important role of PF4 released during platelet activation with the administration of heparin in the pathogenesis of thrombocytopenia and thrombosis in HIT.     

An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients

BACKGROUND: Diagnosis of immune heparin-induced thrombocytopenia (HIT) is usually based on a fall in platelet count below 150 x 109/L (standard definition of thrombocytopenia). However, this definition may be inappropriate for postoperative patients who often develop postoperative thrombocytosis. We sought to determine an improved definition of thrombocytopenia indicating HIT in postoperative orthopedic patients, including its impact on frequency and thrombotic risk of HIT. METHODS: We performed a secondary analysis of a clinical trial of 665 patients who received unfractionated or low-molecular-weight heparin following elective hip arthroplasty. Daily platelet counts and objective studies for deep vein thrombosis were performed in all patients. Laboratory detection of HIT antibodies from a 362-patient subgroup was used to define sensitivity and specificity of various definitions of thrombocytopenia to indicate HIT. RESULTS: The improved definition of HIT was a 50% or greater platelet count fall from the postoperative peak, as this definition had greater sensitivity (50% vs 25%) and similar high specificity (99.1% vs 99.4%) for detecting HIT-IgG compared with the standard definition. Patients with HIT who were identified using the improved definition had a higher frequency of thrombosis than patients without HIT (72.2% vs 17.3%; P<.001). The improved definition showed an even greater absolute difference in frequency of HIT between unfractionated and low-molecular-weight heparin (4.8% vs 0.6%; P<.001) compared with the standard definition (2.7% vs 0%; P =.002). CONCLUSION: A 50% or greater fall in the platelet count from the postoperative peak is a sensitive definition indicating possible HIT that is associated with an increased risk of thrombosis.     

Heparin-induced thrombocytopenia in hemodialysis. Case report and review of the literature

Thrombocytopenia is a potential complication of heparin therapy. There are two forms of heparin-induced thrombocytopenia (HIT). Type-I HIT is characterized by a mild decrease in platelet count that occurs within the first 2-4 days after heparin initiation. The platelet count often returns to normal without stop heparin treatment. The mechanism of thrombocytopenia appears to be due to a direct effect of heparin on platelet activation. The second form (type-II) is an immune-mediated disorder characterized by severe thrombocytopenia, which may include both arterial and venous thrombosis. We present a case of type-II HIT occurred in a hemodialysis patient resulting in acute pulmonary embolism and peripheral venous thrombosis, and review the literature.     

Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin

STUDY OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with a decrease of platelet counts that usually begins after at least 5 days of heparin treatment. Uncertainty exists about the risk of early onset of HIT (ie, < 5 days) in relation to previous heparin exposure. We therefore analyzed the temporal pattern of thrombocytopenia in patients with laboratory-confirmed HIT to assess whether patients with previous heparin exposure have an increased risk of early onset of HIT. DESIGN: Platelet count patterns in patients with a laboratory-confirmed diagnosis of HIT were examined in a retrospective chart review of a clinical study database. The onset of thrombocytopenia < 100 x 10(9)/L associated with the current heparin treatment (mainly unfractionated heparin) was analyzed using nonparametric maximum likelihood estimation. RESULTS: A total of 119 patients with 125 treatment episodes were assessed: HIT developed in 79 patients during initial exposure to heparin, and in 46 patients during reexposure. Early onset (< 5 days) of thrombocytopenia was associated with very recent heparin exposure. Patients reexposed to heparin within 3 months had an earlier onset of thrombocytopenia as compared to patients reexposed to heparin after 3 months (4.9 +/- 4.4 days vs 11.5 +/- 5.5 days [mean +/- SD], p = 0.001). There was no difference between onset on thrombocytopenia < 100 x 10(9)/L in patients reexposed to heparin within 3 to 12 months and after 1 year (9.7 +/- 6.4 days vs 12.3 +/- 5.2 days, p = 0.41). Whether platelet counts were obtained daily or less regularly did not affect the analysis. CONCLUSION: Early onset of thrombocytopenia in HIT is associated with recent heparin treatment (< 3 months). In contrast, for patients who did not receive heparin within the previous 3 months, HIT is an unlikely explanation for thrombocytopenia that occurs within the first 5 days.     

Heparin-induced thrombocytopenia

Thrombocytopenia is a common adverse effect of heparin therapy. Two types of heparin^linduced thrombocytopenia (HIT) are observed clinically - an early onset mild thrombocytopenia (Type I) in which the patients remain asymptomatic and a delayed onset severe thrombocytopenia (Type II). Patients with Type II HIT have an increased risk of thrombotic complications which frequently cause crippling disability e.g. limb amputation or even death. Type I HIT, the commoner of the two types, is believed to be due to the platelet proaggregating effect of heparin itself but Type II HIT is generally agreed to be caused by an immune mechanism, in which heparin-antibody complexes bind to platelets resulting in platelet activation, reduced platelet survival, thrombocytopenia and, in some cases, thrombosis. The diagnosis of HIT is made mainly on a clinical basis but in patients with suspected Type II HIT, laboratory test for the heparin-dependent antibody using platelet aggregometry or the two-point ¹⁴C-serotonin release method, allows confirmation of the diagnosis. In most Type I and all Type II patients, heparin should be stopped and warfarin commenced if there is a recent or new thrombosis requiring continuing anticoagulation. An alternative antithrombotic drug such as low molecular weight heparinoid (Org 10172) or dextran should be given at the same time until warfarin becomes therapeutic. The use of low molecular weight heparins (e.g. Fragmin) should be avoided unless it can be demonstrated that the HIT antibody does not cross-react with these drugs. (Aust NZ J Med 1992; 22: 145–152.)     

Risk of heparin-induced thrombocytopenia in patients receiving thromboprophylaxis

Heparin-induced thrombocytopenia (HIT) is a clinicopathological syndrome associated with heparin therapy that is characterized by a decrease in platelet counts and/or the development of a new thrombosis. Two types of HIT exist, type I is nonimmune and self-resolves, whereas type II is immune-mediated and clinically important. The formation of antibodies against the platelet factor 4-heparin complexes results in platelet activation and thrombin formation, which lead to an increased risk of thrombosis. Unfractionated heparin is associated with a higher risk of HIT than low-molecular-weight heparins. Surgical patients, particularly those undergoing orthopedic or cardiac surgery, are at higher risk of HIT than medical patients. Treatment of HIT involves heparin cessation together with anticoagulation with direct thrombin inhibitors or indirect factor Xa inhibitors.     

Heparin-induced thrombocytopenia: analysis of risk factors in medical inpatients

Heparin-induced thrombocytopenia (HIT) is an unpredictable reaction to heparin characterized by thrombocytopenia and increased risk of life-threatening venous and/or arterial thrombosis. Data are lacking regarding additional risk factors that may be associated with the development of HIT. This study aimed to identify the risk factors that may be associated with HIT in medical inpatients receiving heparin. Twenty five thousand six hundred and fifty-three patients admitted to the medicine service who received heparin product were reviewed retrospectively. The diagnosis of HIT was confirmed if the platelet count dropped >50% from baseline and there was a positive laboratory HIT assay. Fifty-five cases of in-hospital HIT were observed. Multivariate analysis identified the administration of full anticoagulation dose with unfractionated heparin or exposure to heparin products for more than 5 d with an increased risk of HIT. Moreover, patients who were on haemodialysis, carried a diagnosis of autoimmune disease, gout or heart failure were also at increased risk. The results suggest that when using heparin products in these patient cohorts, increased surveillance for HIT is necessary.     

The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 +/- 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n = 360) or therapeutic (n = 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.     

Have You Been HIT?

This review is specifically designed to aid the vascular surgeon in the management of heparin-induced thrombocytopenia (HIT). Heparin-induced thrombocytopenia is a rare complication of heparin administration, which poses significant morbidity and mortality. Its onset is usually 5 to 10 days after the heparin administration and should be suspected if platelet counts drop by at least 50%. Confirmation is given by the presence of HIT antibodies on an enzyme-linked immunosorbent assay (ELISA) or in functional platelet activation assays. The major complication is thrombosis and surprisingly bleeding is rare. Heparin must be stopped immediately if there is a clinical suspicion of HIT and alternative anticoagulation must be started. Anticoagulation is required for at least 2 to 3 months to prevent recurrence of thrombosis. Oral anticoagulation with warfarin should not be initiated until the platelet count has been recovered and there should be an overlap of at least 5 days between starting warfarin and stopping the alternative anticoagulant.     

Heparin-induced thrombocytopenia: recent experience in a large teaching hospital

Background: Heparin‐induced thrombocytopenia (HIT) is a potentially serious adverse reaction caused by platelet‐activating antibodies. Aim: To describe experience with HIT. Methods: Twenty‐two patients identified by laboratory records of heparin‐associated antibodies with a 50% or greater decrease in platelet count were reviewed in our 600‐bed metropolitan teaching hospital from 1999 to April 2005. Results: There was an increase in the frequency of HIT diagnosed during the review period, which was associated with a rise in the number of requests for HIT antibodies. Thrombotic complications were identified in 14 of 22 patients with HIT. Mean age was 65 years, and 11 patients were men. Seven patients died and HIT was considered contributory in four. One patient required mid‐forearm amputation. Unfractionated heparin was used in all cases and five patients also received enoxaparin. Mean time to HIT screen, reflecting when the diagnosis was first suspected, was 14 days. Platelet nadir ranged from 6 × 10⁹/L to 88 × 10⁹/L, with a percentage drop in platelet count of 67–96%. Alternative anticoagulation (danaparoid) was not used in three patients, two of whom died. Conclusions: HIT is a potentially life‐threatening complication of heparin therapy, associated with a fall in platelet count and a high incidence of thromboembolic complications. It is most frequently seen using unfractionated heparin therapy. The increase in frequency of HIT diagnosed in our hospital appears to be associated with a greater awareness of the entity, although detection is often delayed. Platelet count should be monitored in patients on heparin and the presence of antiplatelet antibodies determined if HIT is suspected. Treatment involves both discontinuation of heparin and the use of an alternative anticoagulant such as danaparoid because of the persisting risk of thrombosis.     

PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model

Heparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.     

Heparin-induced thrombocytopenia

BACKGROUND AND OBJECTIVE: There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight and asymptomatic reduction in platelet count, occurring in the first 1-2 days of therapy, that resolves spontaneously; in contrast, HIT II, which has an immunologic origin, is characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withdrawal. HIT II is the most frequent and dangerous side-effect of heparin therapy; in fact, in spite of thrombocytopenia, it can be complicated by venous and arterial thrombosis. Therefore, the recognition of HIT II may be difficult due to the underlying thrombotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical guidelines for the clinical diagnosis and treatment of HIT II. STATE OF THE ART: The prevalence of HIT II, as confirmed by laboratory tests, seems to be about 2% in patients receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The immunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-heparin/ PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-heparin/PF4 immunocomplex activates platelets mainly through binding with the FcgRIIa (CD32) receptor. The onset of thrombocytopenia is independent of the dosage, schedule and route of administration of heparin. Orthopedic and cardiovascular surgery patients receiving post-surgical prophylaxis or treatment for deep venous thrombosis are at higher risk of HIT II. Besides thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses which carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-dependent antibodies. Functional tests, such as platelet aggregation and (14)C-serotonin release assay and immunologic tests, such as the search for anti-PF4/heparin complex antibodies by an ELISA method are available. If HITT II is probable, heparin must be immediately suspended and an alternative anticoagulant therapy should be initiated before resolution of thrombocytopenia and the following treatment with a vitamin K antagonist. The general opinion is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direct thrombin inhibitors such as hirudin. PERSPECTIVES: Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors that induce the occurrence of thrombotic complications. The best therapeutic strategy remains to be confirmed in larger clinical trials.     

Heparin-induced thrombocytopenia

Hemorrhage is the most common and best-recognized complication of heparin treatment. However, a potentially more dangerous complication is the development of heparin-induced thrombocytopenia (HIT). All patients exposed to heparin, irrespective of the dose and route of administration, are at risk of developing HIT. It is due to the formation of antibodies against the heparin-platelet factor 4 complex, which cause secondary activation of platelets, coagulation and, finally, increased thrombin production. The main symptom is the sudden onset of thrombocytopenia involving a drop in the platelet count to less than 50% of the basal level, with or without the appearance of thrombotic complications some 5 to 14 days after the start of heparin therapy. Heparin-induced thrombocytopenia can be detected early in patients receiving heparin by monitoring the platelet count. Demonstration of heparin-dependent platelet activation using an antigen or functional assay confirms the clinical diagnosis. Once the diagnosis of HIT has been confirmed serologically or there is a high level of suspicion of HIT, heparin must be suspended and treatment with an alternative anticoagulant should be considered. This review contains a discussion of the diagnosis and treatment of this syndrome.     

Laboratory diagnosis of heparin-induced thrombocytopenia: advantages of a functional flow cytometric test in comparison to the heparin-induced platelet-activation test

Nearly one third of patients with heparin-induced thrombocytopenia (HIT) will progress to overt thrombosis. Owing to the severity of HIT, a reliable prompt diagnosis is mandatory. In this study 248 consecutive samples from patients referred to our laboratory for HIT diagnosis and 97 specimens from normal controls were prospectively evaluated in parallel using the heparin-induced platelet aggregation (HIPA) test and a flow cytometric (FC) test. The HIPA test resulted in 214 negative, 17 indeterminate and 17 positive samples of patients. The FC method detects activated platelets induced by heparin-immune complexes using the highly sensitive recombinant probe annexin V and pooled platelets from multiple donors. The criteria for positive FC test results included an increase in platelet activiation of at least 11% at 0.3 IU/mL heparin concentration in the tube, and a ratio of more than 1.5 between platelet activation at 0.3 and 200 IU/mL heparin. According to the cut-off level 17 patients who showed indeteminate HIPA test results had 14 negative and 3 indeterminate corresponding FC test results. Only one of these patients (HIPA test indeterminate, FC test indeterminate) had no other obvious medical cause for thrombocytopenia than HIT. Infections or inflammations did not show any association with the FC test results, whereas thromboembolic events displayed a significant patelet activation at pharmacological heparin concentration. Therefore the FC test is associated to the complications of HIT. In conclusion, the FC test, which is fast and practical, showed a good agreement with the HIPA test and may be an accurate and useful test for HIT.     

Current agents for the treatment of patients with heparin-induced thrombocytopenia

Several counterintuitive treatment paradoxes complicate the management of immune heparin-induced thrombocytopenia (HIT). For example, simple discontinuation of heparin often fails to prevent subsequent HIT-associated thrombosis. Thus, current treatment guidelines recommend substituting heparin with a rapidly acting alternative anticoagulant (eg, danaparoid, lepirudin, or argatroban) even when HIT is suspected on the basis of thrombocytopenia alone ("isolated HIT"). Another paradox-coumarin (warfarin) anticoagulation-can lead to venous limb gangrene in a patient with HIT-associated deep-vein thrombosis. Thus, warfarin is not recommended during acute thrombocytopenia secondary to HIT. However, warfarin can be given as overlapping therapy with an alternative anticoagulant, provided that (1) initiation of warfarin is delayed until substantial platelet count recovery has occurred (to at least above 100 x 10(9)/L); (2) low initial doses of warfarin are used; (3) at least 5 days of overlapping therapy are given; and (4) the alternative agent is maintained until the platelet count has normalized. It has recently been recognized that HIT antibodies are transient and usually do not recur upon subsequent re-exposure to heparin. This leads to a further paradox-patients with previous HIT can be considered for a brief re-exposure to heparin under exceptional circumstances; for example, heart surgery requiring cardiopulmonary bypass, if HIT antibodies are no longer detectable using sensitive assays. For patients with acute or recent HIT who require urgent heart surgery, other approaches include use of alternative anticoagulants (eg, lepirudin or danaparoid) for cardiopulmonary bypass or antiplatelet agents (eg, tirofiban or epoprostenol) to permit intraoperative use of heparin.     

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a syndrome of antibody-mediated activation of platelets and coagulation that confers increased risk for thrombosis. This article reviews recent studies of the pathogenesis, laboratory testing, frequency, and clinical presentation of HIT. Topics discussed include the nature of the neoepitopes on platelet factor 4 recognized by HIT antibodies, the nonspecific nature of the polyanions that support neoepitope formation, activation of monocytes and endothelium, and the development of new animal models. The transient "autoimmune" nature of HIT is highlighted in relation to new data concerning the rapid decline in HIT antibodies, as well as the recent recognition of a syndrome of "delayed-onset HIT" in which thrombocytopenia and thrombosis begin several days after stopping heparin. Detecting only HIT antibodies of the immunoglobulin G class is suggested as one way to increase diagnostic specificity of laboratory testing. Recent reports suggest that HIT could explain approximately 5% of cases of acute adrenal failure caused by bilateral adrenal hemorrhagic infarction.     

Cerebral venous thrombosis due to essential thrombocythemia and worsened by heparin-induced thrombocytopenia and thrombosis

This case describes the medical history of a 61-year-old woman treated for cerebral venous thrombosis (CVT) leading to diagnosis of essential thrombocythemia (ET). During treatment with unfractionated heparin, after initial improvement of clinical state, signs of cerebral hypertension reappeared. Although the platelet count decreased, heparin-induced thrombocytopenia (HIT) was only suspected 2 days later when it dropped below the standard 150 × 10(9) L(-1) threshold. HIT diagnosis was confirmed by the presence of anti-PF4/heparin IgG. This late finding was the cause of the extension of CVT with worsening of cerebral hypertension necessitating decompressive craniectomy. Elevated basal platelet count due to ET can delay diagnosis and treatment of HIT. In this case, physicians should be more attentive to platelet count variations rather than thrombocytopenia threshold.     

肝素诱导的血小板减少症研究进展

肝素诱导的血小板减少症是一种特异性自身免疫性疾病,是由于抗体对肝素-血小板因子4复合物的识别,损伤了血小板以及内皮细胞而导致,以血小板减少及血栓形成为主要表现,通过4T评分以及实验室检查可有助于诊断,治疗上需要立即停用肝素及其相关制剂并开始替代抗凝治疗。